In this study, our data revealed that knockdown of lnc‐ISG20 could inhibit the renal fibrosis of DN, and lnc‐ISG20 could inhibit the expression of miR‐486‐5p which was further found to be able to inhibit the AKT phosphorylation via NFAT5. Here, NFAT5 is linked to renal fibrosis.